title: Anti-tumor efficacy of a hepatocellular carcinoma vaccine based on dendritic cells combined with tumor-derived autophagosomes in murine models.
abstract: The majority of hepatocellular carcinoma (HCC) patients have a poor prognosis with current therapies, and new approaches are urgently needed. We have developed a novel therapeutic cancer vaccine platform based on tumor cell derived autophagosomes (DRibbles) for cancer immunotherapy. We here evaluated the effectiveness of DRibbles-pulsed dendritic cell (DC) immunization to induce anti-tumor immunity in BALB/c mouse HCC and humanized HCC mouse models generated by transplantation of human HCC cells (HepG2) into BALB/c-nu mice. DRibbles were enriched from H22 or BNL cells, BALB/c-derived HCC cell lines, by inducing autophagy and blocking protein degradation. DRibbles-pulsed DC immunization induced a specific T cell response against HCC and resulted in significant inhibition of tumor growth compared to mice treated with DCs alone. Anti- tumor efficacy of the DCs-DRibbles vaccine was also demonstrated in a humanized HCC mouse model. The results indicated that HCC/DRibbles-pulsed DCs immunotherapy might be useful for suppressing the growth of residual tumors after primary therapy of human HCC.
authors.affiliation: Cancer Research and Biotherapy Center, the Affiliated Nanjing Second Hospital, Medical School of Southeast University, Nanjing, Jiangsu, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Su
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.forename: Meng
authors.initials: M
authors.lastname: Xue
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Ding
authors.forename: Meng
authors.initials: M
authors.lastname: Cao
authors.forename: Zhen-Xian
authors.initials: ZX
authors.lastname: Zhou
authors.forename: Hong-Min
authors.initials: HM
authors.lastname: Hu
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000378:metabolism; D008113:Liver Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010588:Phagosomes; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D019496:Cancer Vaccines; D007371:Interferon-gamma